Childhood Leukemia: An Ounce of Prevention

Written by Mark Miller MD, MPH; Catherine Metayer, MD, PhD; and Gary Dahl, MD

Mark Miller, MD, MPH
Catherine Metayer, MD, PhD

This post was originally published on the website of Physicians for Social Responsibility. It is posted here with permission of the authors. CHE is hosting a teleconference call on January 22nd on this topic as part of the launch of A Story of Health. The call features Dr. Miller and Dr. Metayer, the first two authors of this post.

The nearly miraculous news is that great strides have been made in the treatment of childhood acute lymphocytic leukemia, and now nearly 90% of children are cured. The dark side, however, is that the incidence of childhood leukemia (age 0-14 years) in the United States has increased an average of 0.7 percent per year since 1975.[1] During the 35 years between 1975 and 2011, there has been a 55% increase in the number of children diagnosed annually (per capita, age adjusted) with this most common form of cancer in childhood. Though a cure is now expected for most children, side effects both short and long-term and secondary cancers later in life are common. The emotional and financial costs for these children and families is considerable.

Childhood leukemia is difficult to study because it is relatively rare. Nevertheless, substantial evidence identifying a number of risk factors has emerged over the past two decades. This growing body of literature has implicated the potential role of environmental hazards in the etiology of childhood leukemia. Exposures to ionizing radiation, solvents, pesticides, and tobacco smoke have consistently demonstrated positive associations with the risk of developing childhood leukemia. A recent meta-analysis of 15 studies found exposure during pregnancy to unspecified pesticides,  herbicides, or insecticides to be associated, respectively, with more than a 50%, 60%,  and 100% increased risk for developing childhood leukemia.[2]

In order to examine potential risk factors for this rare disease, an international collaborative called the Childhood Leukemia International Consortium (CLIC) was established in 2007 to pool data from independent studies investigating environmental exposures, gene–environment interactions, and subtype-specific associations.[3] Pooled data from 1,329 cases demonstrated a near doubling of risk for acute myeloid leukemia in children whose mothers were occupationally exposed to pesticides during pregnancy  (OR 1.94 ; 95% CI 1.19, 3.18)[4]. Children born to fathers who were occupationally exposed to pesticides around the time of conception had a 20% increased risk of developing acute lymphoblastic leukemia (ALL) (95% CI 1.06, 1.38).

Paternal tobacco use, especially around the time of conception, is associated with increased risk in many studies. These studies likely indicate germ cells being affected[5] [6]. A meta-analysis by Milne found a 40% increase in risk (95% CI: 1.24, 1.68) for children of fathers who smoked more than 20 cigarettes/day around conception[5]. A study from our group indicates the highest risk results when paternal peri-conception/prenatal smoking is combined with early childhood exposure to secondhand smoke.[7]

Exposure to paints and solvents during pregnancy are also associated with increased risk. Surrogate measures of exposure (e.g., living near a gas station, high exposure to traffic-related pollutants) to benzene a recognized leukemogen in adults also are associated with increased risk. A recent meta-analysis performed by the CDC suggests that living near highly trafficked roadways after birth increases a child’s risk for leukemia by more than 50% (OR 1.53; 95% CI.1.12, 2.10)[8].

Other exposures have been found to be protective. A large pooled analysis of twelve studies of childhood leukemia from ten countries found vitamin or folate supplementation before or during pregnancy was associated with 15% (95% CI: 0.78-0.92) and 20% (95% CI: 0.71-0.89) reduction in risk, respectively.

With this accumulating evidence of risk factors and possible preventive factors of childhood leukemia, why are there no programs for childhood leukemia prevention? Worse, misleading information from respected sources fails to acknowledge the current state of the evidence. The American Cancer Society, for example, clearly states on its website, “there is no known way to prevent most childhood cancers at this time. Most adults and children with leukemia have no known risk factors, so there is no sure way to prevent their leukemias from developing.”[9] The CDC Division of Cancer Prevention and Control, on their website, discusses exposures of children and adolescents in regards to prevention of cancers later in life but says nothing about preventing childhood cancer. Pediatric oncologists tell us that they have had little training in environmental risk factors and childhood cancer[10]. Their focus is on treatment and cure rather than prevention.

We believe the reason no steps toward prevention of childhood leukemia have been taken thus far is the reluctance to attribute environmental factors as causative. This is due, in part, to the high bar required to reach consensus on causation. Double blinded randomized studies would be unethical. Prospective cohort studies with adequate power to evaluate rare diseases such as childhood leukemia will require major international collaboration involving large national studies such as the International Childhood Cancer Cohort Consortium[11].

All of the risk factors associated with childhood leukemia (ie. pesticides, tobacco, solvents, air pollution) are also associated with various other important health impacts. Thus, associations with leukemia are yet one more reason (though one that gets attention) to advise cautious avoidance and strengthen regulatory programs aimed at reducing harmful exposures.

In their paper on smoking, breast cancer and the increasing cost of caution, Glantz and Johnson cite the findings of the Surgeon General’s Report on Smoking and Health of 1964[12] [13]. Though the report stopped short of finding that smoking caused cardiovascular disease, it concluded that nevertheless, action was warranted:

Although the causative role of cigarette smoking in deaths from coronary disease is not proven, the Committee considers it more prudent from the public health viewpoint to assume that the established association has causative meaning than to suspend judgment until no uncertainty remains.”

It is time that we utilize the hard-won accumulating knowledge in children’s environmental health to begin fostering prevention activities, including those targeted at the prevention of childhood leukemia.

[1] Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, et al.,  (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.

[2] Turner MC, Wigle DT, and Krewski D. Residential pesticides and childhood leukemia: a systematic review and meta-analysis. Environmental Health Perspectives 2010 118 (1):33-41.

[3] Metayer C, Milne E, Clavel J, Infante-Rivard C, Petridou E, Taylor M, Schüz J, et al. The Childhood Leukemia International Consortium. Cancer Epidemiol. 2013 Jun;37(3):336-47.

[4]  Bailey HD, Fritschi L, Infante-Rivard C, Glass DC, Miligi L, Dockerty JD, Lightfoot T, et al. Parental occupational pesticide exposure and the risk of childhood leukemia in the offspring: Findings from the childhood leukemia international consortium..Int J Cancer Mar 19, 2014

[5] Milne E, Greenop KR, Scott RJ, Bailey HD, Attia J, Dalla-Pozza L, de Klerk NH, Armstrong BK.  Parental prenatal smoking and risk of acute lymphoblastic leukemia. Am J Epidemiol. 2012 Jan 1;175(1):43-53

[6] Liu R, Zhang L, McHale CM, Hammond SK. J Oncol. 2011. Epub 2011 May 29.

[7] Metayer C, Zhang L, Wiemels JL, Bartley K, Schiffman J, Ma X,  et al. Tobacco smoke exposure and the risk of childhood acute lymphoblastic and myeloid leukemias by cytogenetic subtype. Cancer Epidemiol Biomarkers Prev. 2013 Sep;22(9):1600-11.

[8] Boothe VL, Boehmer TK, Wendel AM, Yip FY. Residential Traffic Exposure and Childhood Leukemia A Systematic Review and Meta-analysis. Am J Prev Med 2014;46(4):413–422.

[9] American Cancer Society, accessed June 2, 2014.

[10] “Translating Research in Environmental Health to Pediatric Practice: A Survey of Pediatric Hematologists and Oncologists” Miller , Zachek, Dahl, Su , Buffler. Poster at Protecting Children’s Health for a Lifetime, Annual Children’s Environmental Health Research Centers Meeting, October 2013. Washington DC.

[11] Cohort profile: the International Childhood Cancer Cohort Consortium (I4C). Brown RC, Dwyer T, Kasten C, Krotoski D, Li Z, Linet MS, Olsen J, Scheidt P, Winn DM; International Childhood Cancer Cohort Consortium (I4C) nt J Epidemiol. 2007 Aug;36(4):724-30.

[12]  Glantz and Johnson. The surgeon general report on smoking and health 50 years later: breast cancer and the cost of increasing caution. Cancer Epidemiol Biomarkers Prev 2014;23:37-46.

[13] U.S. Public Health Service. Smoking and health: report of the Advisory Committee to the Surgeon General of the Public Health Service. Washington, DC: U.S. Public Health Service; 1964.

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